Effects of Dmiro Isoforms on Mitochondrial Transport, Health, and Morphology

Abstract

Microtubule (MT)-based transport of mitochondria into dendrites and axons is vital for sustaining neuronal excitation and synaptic function. The mitochondrial GTPase Miro is critical for mitochondrial transport by linking MT motor proteins to mitochondria. In flies and mammals, Miro proteins contain a variable domain whose position but not sequence is highly conserved. In Drosophila, the shortest (Miro-S) and longest (Miro-L) isoform differ by only 21 amino acids while the medium isoform (Miro-M) is 8 amino acids shorter than Miro-L. To test the functional significance of these isoforms, we expressed each individually in miro null or wild type Drosophila neurons and found differential effects on mitochondrial transport, structure and health. Expression of Miro-L and -S fail to rescue the larval lethality of miro null mutants while Miro-M does. OE of Miro-L and -S but not -M is also lethal. The effects on viability correlate with effects on mitochondria. Miro-L and Miro-S primarily cause morphological changes of axonal mitochondria, and are less efficient in facilitating aspects of mitochondrial transport than Miro-M. In conclusion, our data suggest different roles and/or activities for each of the 3 Miro protein isoforms.